A study in the total synthesis of natural products which have antitumor properties, and analogs of such compounds, is proposed. A key element of the plan is to use activated cyclopropanes to achieve synthetic access to such systems. The particular natural products are described below. The mitomycins will be pursued both from the standpoint of total synthesis and with the objective of generating new analog structures for biological evaluation. These compounds are in experimental clinical use. The pyrrolizidine alkaloids constitute another objective. Particular emphasis will be placed on achieving stereochemical and regiochemical control over the necine bases and unsaturated necine bases. In the latter class, retronecine is the basic component of the antitumor agent indicine N-oxide. (N.S.C. 132319). It is hoped that synthesis will produce compounds, which upon biological evaluation, will provide focus for the effects of structure upon biological function. A disconnective logic is proposed to reach the novel tumor inhibitor coriolin. Quick access to the basic ring system is envisioned, utilizing intramolecular phenoxy nucleophiles. A synthetic program designed to provide structural definition to the source of activity of the antineoplastic agent camptothecin will be pursued. It is felt that this program will define the crucial structural requirements. A program to define the stereochemical requirements for the tumor inhibitors vernolepin and vernomenin is proposed. New analogs involving acrylated alpha'-hydroxyl-alpha-methylenelactones will be synthesized to attempt to identify the basic structural features for antitumor activity.